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Biomedical subjects

A Hall

Publications and source records attributed to A Hall.

At least 199 records · Page 11Linked to original sources
PubMed1995

Long-term efficacy of continuing hepatitis B vaccination in infancy in two Gambian villages.

In 1984, all non-immune children under the age of 5 years in the Gambian villages of Keneba and Manduar were vaccinated against hepatitis B virus (HBV). All children born in these villages since 1984 have been vaccinated in infancy. Despite a rapid fall in antibody concentrations, vaccine efficacy against HBV infection and chronic carriage of HBsAg has increased with time. Overall, vaccine efficacies in 1993 against HBV infection and chronic HBsAg carriage were 94.7% (95% Cl 93.0-96.0) and 95.3% (91.0-97.5), respectively. Breakthrough infections in vaccinated children largely originate from chronic HBsAg carriers. Thus, we tested 261 chronic carriers for HBV DNA and e antigen. The prevalence of these markers of infectivity, and the amount of HBV DNA, decreased greatly with age. Detailed studies of breakthrough infections over two 4-year periods revealed that in the second period there were fewer than half the expected numbers of infections. Our findings suggest that in Keneba and Manduar long-term vaccination is progressively decreasing HBV transmission by chronic carriers, since their infectivity diminishes with time.

Adolescent↗
PubMed1995

Direct involvement of the small GTP-binding protein Rho in lbc oncogene function.

The lbc oncogene is tumorigenic in nude mice, transforms NIH 3T3 fibroblasts, and encodes a Dbl homology domain found in several transforming gene products including the dbl oncogene product. While both lbc- and dbl-transformed NIH 3T3 foci exhibited a comparable gross appearance, lbc-transformed cell morphology was clearly distinct from that of dbl-transformed cells. Given these differences, we investigated the biochemical activity and target specificity of the Lbc oncoprotein both in vivo and in vitro. Here we show that Lbc associates specifically with the GTP-binding protein Rho in vivo, but not with the Ras, Rac, or Cdc42Hs GTP-binding proteins, and that recombinant, affinity-purified Lbc specifically catalyzes the guanine-nucleotide exchange activity of Rho in vitro. Consistent with an in vivo role for Lbc in Rho regulation, we further demonstrate that micro-injected onco-lbc potently induces actin stress fiber formation in quiescent Swiss 3T3 fibroblasts indistinguishable from that induced by Rho. Finally, lbc-induced NIH 3T3 focus formation is inhibited by co-transfection with a rho dominant-negative mutant. These results strongly indicate that the lbc oncogene encodes a specific guanine nucleotide exchange factor for Rho and causes cellular transformation through activation of the Rho signaling pathway.

3T3 Cells↗
PubMed1995

Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia.

Rho and rac, two members of the ras-related superfamily of small GTPases, regulate the polymerization of actin to produce stress fibers and lamellipodia, respectively. We report here that cdc42, another member of the rho family, triggers the formation of a third type of actin-based structure found at the cell periphery, filopodia. In addition to stress fibers, rho controls the assembly of focal adhesion complexes. We now show that rac and cdc42 also stimulate the assembly of multimolecular focal complexes at the plasma membrane. These complexes, which are associated with lamellipodia and filopodia, contain vinculin, paxillin, and focal adhesion kinase, but are distinct from and formed independently of rho-induced focal adhesions. Activation of cdc42 in Swiss 3T3 cells leads to the sequential activation of rac and then rho, suggesting a molecular model for the coordinated control of cell motility by members of the rho family of GTPases.

3T3 Cells↗
PubMed1995

Structural basis for the biological specificity of cystatin C. Identification of leucine 9 in the N-terminal binding region as a selectivity-conferring residue in the inhibition of mammalian cysteine peptidases.

The structural basis for the biological specificity of human cystatin C has been investigated. Cystatin C and other inhibitors belonging to family 2 of the cystatin superfamily interact reversibly with target peptidases, seemingly by independent affinity contributions from a wedge-shaped binding region built from two loop-forming inhibitor segments and a binding region corresponding to the N-terminal segment of the inhibitor. Human cystatin C variants with Gly substitutions for residues Arg-8, Leu-9, and/or Val-10 of the N-terminal binding region, and/or the evolutionarily conserved Trp-106 in the wedge-shaped binding region, were produced by site-directed mutagenesis and Escherichia coli expression. A total of 10 variants were isolated, structurally verified, and compared to wild-type cystatin C with respect to inhibition of the mammalian cysteine peptidases, cathepsins B, H, L, and S. Varying contributions from the N-terminal binding region and the wedge-shaped binding region to cystatin C affinity for the four target peptidases were observed. Interactions from the side chains of residues in the N-terminal binding region and Trp-106 are jointly responsible for the major part of cystatin C affinity for cathepsin L and are also of considerable importance for cathepsin B and H affinity. In contrast, for cathepsin S inhibition these interactions are of lesser significance, as reflected by a Ki value of 10(-8) M for the cystatin C variant devoid of Arg-8, Leu-9, Val-10, and Trp-106 side chains. The side chain of Val-10 is responsible for most of the affinity contribution from the N-terminal binding region, for all four enzymes. The contribution of the Arg-8 side chain is minor, but significant for cystatin C interaction with cathepsin B. The Leu-9 side chain confers selectivity to the inhibition of the target peptidases; it contributes to cathepsin B and L affinity by factors of 200 and 50, respectively, to cathepsin S binding by a factor of 5 only, and results in a 10-fold decreased affinity between cystatin C and cathepsin H.

Amino Acid Sequence↗
PubMed1995

A novel type of myosin implicated in signalling by rho family GTPases.

A novel widely expressed type of myosin (fifth unconventional myosin from rat: myr 5) from rat tissues, defining a ninth class of myosins, was identified. The predicted amino acid sequence of myr 5 exhibits several features not found previously in myosins. The myosin head domain contains a unique N-terminal extension and an insertion of 120 amino acids at a postulated myosin-actin contact site. Nevertheless, myr 5 is able to bind actin filaments in an ATP-regulated manner. The head domain is followed by four putative light chain binding sites. The tail domain of myr 5 contains a region which coordinates two atoms of zinc followed by a region that stimulates GTP hydrolysis of members of the ras-related rho subfamily of small G-proteins. Myr 5 therefore provides the first direct link between rho GTPases which have been implicated in the regulation of actin organization and the actin cytoskeleton. It is also the first unconventional myosin for which a tail binding partner(s), namely members of the rho family, has been identified.

Actins↗
PubMed1995

14-3-3 proteins. Hot numbers in signal transduction.

14-3-3 proteins have been known about for a long while but their functions have been poorly understood; recent results indicate that they play a role in both signal transduction and the cell cycle.

14-3-3 Proteins↗
PubMed1995

Evaluation of digestive proteinases from the Antarctic krill Euphasia superba as potential chemonucleolytic agents. In vitro and in vivo studies.

Chemonucleolysis is a therapeutic procedure whereby a degradative enzyme is injected intradiscally to reduce disc height/width by depolymerisation of extracellular matrix components. This process is considered to diminish disc pressure on inflamed nerve roots, resulting in the alleviation of sciatic pain. In the present study two krill (Euphasia superba) enzyme preparations, a proteinase and an esterase preparation, were evaluated for their potential as chemonucleolytic agents. Initially, their ability to degrade several protein (azocoll, casein, proteoglycans, PGs) and peptide (CBZ-arg-4-nitroanilide, CBZ-lys-thiobenzyl ester) substrates was assessed in vitro. The krill proteinase preparation rapidly converted azocoll, casein and PGs to small peptides. Furthermore, when this degradative enzyme preparation was evaluated in vivo, a relatively low intradiscal dose (0.54 mg/disc) was found to reduce intervertebral disc widths in beagles to 48% +/- 10.5% (mean +/- SEM) of their pre-injection values within 2 weeks of administration. Moreover, the discs injected with this proteinase had reconstituted up to 80% +/- 9% (mean +/- SEM) of their pre-injection widths at the termination of the experiment (32 weeks). These data suggest that the krill protease preparation has potential as a chemonucleolytic agent which would allow disc matrix reconstitution. Conversely, the krill esterase preparation also degraded PGs, but into relatively large fragments. This limited digestion of PGs indicates that the krill esterase would be a less effective chemonucleolytic agent than the corresponding proteinase.

Animals↗
PubMed1995

Serum concentrations of von Willebrand factor and soluble thrombomodulin indicate alteration of endothelial function in inflammatory bowel diseases.

Serum concentrations of immunoreactive von Willebrand factor (vWF) and soluble thrombomodulin (TM), and vWF multimer patterns were measured to assess endothelial function in patients with inflammatory intestinal diseases. In Crohn's disease and acute infective diarrhea, vWF concentrations were significantly higher than in normal controls. In all patient groups, multimeric analysis of vWF and the concentration of serum TM were not different from normal controls. The results indicate alteration of endothelial function in inflammatory intestinal disorders. They may be compatible with the presence of localized vasculitis, but indicate that systemic endothelial destruction does not occur in inflammatory bowel disease.

Colitis, Ulcerative↗
PubMed1995

The Rho's progress: a potential role during neuritogenesis for the Rho family of GTPases.

Growth cones navigate by coupling extracellular guidance cues to directed outgrowth of the actin cytoskeleton through cyclical extension of filopodia and lamellipodia, but the biochemical basis of this coupling is at present unknown. Recent studies have shown that members of the Rho family of small GTPases regulate the formation of filopodia, lamellipodia and stress fibres in fibroblasts, and there are striking morphological similarities between spreading fibroblasts and advancing growth cones. This resemblance suggests that the Rho family of proteins could be the link between incoming signals and the regulation of both actin dynamics and cell-substratum adhesion in the neuronal growth cone.

Actins↗
PubMed1995

A clinical study of pulsed Nd: YAG laser-induced pulpal analgesia.

The pulsed Nd: YAG laser is advocated as an alternative means of providing analgesia during routine dental procedures. Since the evidence to support this claim is mainly anecdotal, a clinical trial was carried out using an electric pulp tester (EPT) to measure the extent and duration of any analgesic effect induced by pulsed Nd: YAG laser treatment. A double-blind crossover experiment involving laser and sham treatments was used on 21 subjects. A small (3.6 arbitrary units) but statistically significant increase was observed in the mean responses measured 5 min after laser treatment with 113 mJ pulses at 15 pulses s-1 (pps) for 3 min. The pain thresholds returned to baseline values after 60 min. No statistically significant changes in threshold were found with the sham treatment. The order in which laser and sham treatment was received made no difference to the results.

Adult↗
PubMed1995

Morbilliviruses in aquatic mammals: report on round table discussion.

A workshop was organised to ascertain the current situation with regard to morbillivirus infections in aquatic animals. The great interest generated by the discovery of these new virus infections in 1988 has to some extent abated but much high quality research has continued in this field as the workshop showed. There is some serological evidence that the viruses have continued to circulate in most areas since the initial epizootics. As to their origin, it appears that the most likely source of the European seal morbillivirus (PDV-1) is the North Atlantic and Artic seal populations. As to the origin of the Mediterranean dolphin morbillivirus and the morbilliviruses isolated from porpoises, there is serological evidence that the viruses are widespread in many cetacean species in the Atlantic and 93% of long-finned pilot whales (Globicephala melas) which mass stranded between 1982 and 1993 were morbillivirus seropositive. The epizootic in freshwater seals in Lake Baikal was unrelated to events in the European marine mammal populations. The virus which infected these animals (PDV-2) is indistinguishable from canine distemper field strains. Serological and molecular biological studies provided evidence for the presence of the virus in the seals, at least as late as the Summer of 1992 when the animals were last sampled.

Animals↗
PubMed1995

The influence of audiotapes on patient participation in the cancer consultation.

This study examined the effect of providing patients with an audiotape of a previous consultation on their level of participation during a subsequent consultation. 117 newly referred medical oncology patients randomised to receive a tape (n = 63) or not (n = 54) had two linked consultations which were both audiotaped. A content analysis revealed no significant differences between tape and control group in the mean number of questions asked during the second consultation. However, significantly more tape group patients (77%) asked for clarification of at least one piece of information compared to the control group (57%) (P = 0.04). A larger number of control group patients (61%) made at least one request for facts already provided in their first consultation compared to tape group patients (39%) (P = 0.05). Audiotapes appear to facilitate patients' requests for the clarification of previously given information and permit the re-absorption of complex information given when patients may have been too distressed for it to be assimilated.

Adult↗
PubMed1995

Antibody isotype responses to antigens of Ascaris lumbricoides in a case-control study of persistently heavily infected Bangladeshi children.

Antibody responses to Ascaris lumbricoides worm antigens were examined by ELISA in a case-control study of 2 groups of Bangladeshi children, one of which had been shown over a period of 12 months to be consistently lightly infected (controls) and the other consistently heavily infected (cases). The children showed a wide range in intensity of infection; children identified as cases were on average 4 times more heavily infected than the controls. There were no significant differences in weight, height, mid-upper arm circumference and skinfold thickness between the case or control subjects at the time blood samples for analyses by ELISA were collected. Children with repeatedly heavy infections with A. lumbricoides had higher concentrations of antibody isotypes to the antigens of A. lumbricoides than children who are repeatedly lightly infected. IgG1, IgG4 and IgE to worm antigens occurred in significantly higher concentrations in heavily infected subjects. This suggests that these antibody responses simply reflect the intensity of infection and may not play a significant role in protecting against heavy infections.

Adult↗